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BJA Advance Access originally published online on September 12, 2008
British Journal of Anaesthesia 2008 101(5):659-665; doi:10.1093/bja/aen265
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2008. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Effects of clonidine on lidocaine-induced inhibition of axonal transport in cultured mouse dorsal root ganglion neurones

H. Hiruma1,*, K. Shimizu2, T. Takenami2, H. Sugie1 and T. Kawakami1

1 Department of Physiology
2 Department of Anesthesiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara 228-8555, Japan

* Corresponding author. E-mail: hiruma{at}med.kitasato-u.ac.jp

Background: The {alpha}2-adrenoceptor agonist clonidine is used in combination with lidocaine for anaesthesia. Lidocaine inhibits axonal transport and neurite growth, whereas {alpha}2-adrenoceptor agonists have neurotrophic effects. Here we have investigated whether clonidine reduces lidocaine-induced inhibition of axonal transport in cultured mouse dorsal root ganglion neurones.

Methods: Axonal transport of organelles and neurite growth were assessed by video microscopy in cells treated with clonidine and lidocaine for 1 h. Stable responses were achieved within this period.

Results: Clonidine (10 and 100 µM) increased and lidocaine (10, 100 µM, and 1 mM) decreased axonal transport. The inhibitory effects of lidocaine were reduced by simultaneous treatment with clonidine. The actions of clonidine were antagonized by the {alpha}2-adrenoceptor antagonist yohimbine. Since clonidine was reported to block N-type channels, we further investigated the role of ion channels in the antagonistic action of clonidine on the lidocaine response. The action of lidocaine on axonal transport was not mimicked by the Na+ channel blocker tetrodotoxin and not blocked by the Na+ channel activator veratridine. The action of lidocaine was not blocked by the L-type Ca2+ channel blocker nifedipine, but was blocked by the N-type channel blocker {omega}-conotoxin MVIIA. These effects on axonal transport correlated with the effects on neurite growth.

Conclusions: Inhibition of axonal transport induced by lidocaine, which may be mediated by N-type channel activation, can be blocked by clonidine. Clonidine may alleviate the effects of lidocaine on neuronal dysfunction.

Keywords: anaesthetics local, lidocaine; nerve, somatic; pharmacology, clonidine


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